Studies are in progress to define the pharmacological and toxicological potential of fluoride and fluorine-containing compounds used in fluoridation, hemodialysis, treatment of bone disease, and anesthetics. Studies continue on testing antidotes and treatment procedures in heavy metal poisoning. Work is also in progress on the development of better statistical design for clinical trial. The molecular mechanism of toxicity of the benzo-dioxins is under study, and new methods are being developed to assay the most toxic dioxins as a general screen for environmental contamination by these compounds. Other studies at the cellular and molecular level include the biochemical mechanisms of conversion of nitrites to proximate carcinogens. Measurements of urinary excretion of the enzyme beta-N-acetylglucosaminidase has led to a highly sensitive test for renal toxicity and to the detection of renal damage by therapeutic doses of aspirin. The effects of phenobarbitone and other addicting drugs will be followed on the ultrastructure of the adrenal cortex and on plasma corticosterone. The metabolism and mechanism of action of a variety of other agents are under study, including methotrexate L-asparaginase, methyldopa, L-dopa, chlorothiazide, selenium, and a new organo-fluorine compound, perfluoro-octanoic acid, recently identified in human serum. BIBLIOGRAPHIC REFERENCES: Amin-Zaki, L., Elhassani, S., Majeed, M.A., Clarkson, T.W., Doherty, R.A. and Greenwood, M.R. (1976) Perinatal methylmercury poisoning in Iraq. Am. J. Dis. Child. (in press). Clarkson, T.W. and Marsh, D.O. (1976). The toxicity of methylmercury in man: response relationships in adult populations. In: Effects and Dose-Response Relationships of Toxic Metals, ed. G. Nordberg ASP Biological and Medical Press, Amsterdam. (in press).